CEDOC, Centro de Estudos Doenças Crónicas, Nova Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Lisbon, Portugal.
Adv Exp Med Biol. 2018;1071:83-88. doi: 10.1007/978-3-319-91137-3_10.
Previous data showed the lack of efficacy of an adrenoceptor antagonist to revert hypertension induced by chronic intermittent hypoxia (CIH). We hypothesized that, in addition to sympathetic activation, CIH may change the availability and dynamics of cysteine. Temporal variation in total cysteine and its fractions, free reduced, free oxidized and protein-bound (CysSSP), were measured in homogenates of kidney cortex and medulla of Wistar rats. Animals were exposed to CIH for 14, 21 and 60 days and cysteine fractions and fibronectin gene expression were assessed at these time-points. Two different phases in cysteine dynamics were identified. An early phase (14d) characterized by an increase in cysteine oxidation and CysSSP forms. Late events (>21d) were characterized by a global reduction in cysteine, minimum level of CysSSP and maximum overexpression of fibronectin in kidney cortex. In conclusion, cysteine dynamics is influenced by the duration of CIH exposure: first there is a cysteine disulfide stress-like adaptive response followed by a progressive loss of cysteine availability and a decrease in CysSSP fraction. Kidney fibrosis associated to an unbalance in cysteine dynamics might contribute to the inefficacy of available antihypertensive drugs in patients with delayed diagnosis of sleep apnea.
先前的数据表明，肾上腺素受体拮抗剂对于逆转慢性间歇性低氧（CIH）引起的高血压无效。我们假设，除了交感神经激活之外，CIH 可能会改变半胱氨酸的可及性和动力学。在 Wistar 大鼠肾皮质和髓质匀浆中测量了总半胱氨酸及其分数（游离还原型、游离氧化型和蛋白结合型[CysSSP]）的时间变化。动物暴露于 CIH 14、21 和 60 天，并在这些时间点评估半胱氨酸分数和纤连蛋白基因表达。确定了半胱氨酸动力学的两个不同阶段。早期阶段（14d）的特征是半胱氨酸氧化和 CysSSP 形式增加。晚期事件（>21d）的特征是半胱氨酸全面减少，CysSSP 分数最低，肾皮质中纤连蛋白的最大过表达。总之，半胱氨酸动力学受 CIH 暴露时间的影响：首先是半胱氨酸二硫键应激样适应性反应，随后是半胱氨酸可用性逐渐丧失和 CysSSP 分数下降。与半胱氨酸动力学失衡相关的肾脏纤维化可能导致睡眠呼吸暂停延迟诊断患者现有降压药物无效。
